Recent evidence indicates that transcription arrest or termination sites are situated near the 5' ends of many eukaryotic cellular and viral genes and that transcription through these sites is subject to metabolic or developmental control. The number and diversity of examples suggest that antitermination of transcription is a prevalent mechanism for controlling gene expression in eukaryotic cells. To understand this important gene regulatory process we have chosen to study the expression of the murine and human adenosine deaminase (ADA) genes. Evidence from my laboratory suggests that cell specific regulation of ADA gene expression results from antitermination mechanisms that override or disrupt a transcription termination signal that resides within the 3' end of exon 1. Research proposed here will determine the sequence and factor requirements for the exon 1 transcription termination event and the means by which it is developmentally controlled in a cell specific manner. As a result of proposed experiments we expect to determine: 1) The sequence requirements for transcription termination in exon 1 of the murine and human ADA genes, 2) The role of antitermination mechanisms in the regulation of ADA gene expression, and 3) The protein components affecting transcription termination and antitermination. The results of these experiments should allow us to distinguish among three general models for the control of transcription termination: 1) Modification of the RNA polymerase complex, 2) Modification of RNA secondary structure, and 3) Steric interference of transcription elongation by direct DNA binding. The research proposed here should lead to a better understanding of the mechanism of exon 1 transcription termination and the role of antitermination in the regulation of gene expression in mammalian cells.